Categories: Synthesis of N-Heterocycles >
Synthesis of 4H-1,2,4-triazoles
Triflic anhydride activation followed by microwave-induced cyclodehydration enables a one-pot synthesis of 3,4,5-trisubstituted 1,2,4-triazoles from secondary amides and hydrazides. In addition, the 1,2,4-triazole moiety is shown to be a useful directing group for Ru-catalyzed C-H arylation. A Pd-catalyzed intramolecular C-H functionalization reaction allows access to 1,2,4-triazolophenanthridine.
W. S. Bechara, I. S. Khazhieva, E. Rodriguez, A. B. Charette, Org. Lett., 2015, 17, 1184-1187.
An environmentally benign synthesis of various 3,4,5-trisubstituted 1,2,4-triazoles and N-fused 1,2,4-triazoles via ceric ammonium nitrate catalyzed oxidative cyclization of amidrazones and aldehydes using polyethylene glycol as recyclable reaction medium is economic and potentially viable for commercial applications.
M. Nakka, R. Tadikonda, S. Rayavarapu, P. Sarakula, S. Vidavalur, Synthesis, 2015, 47, 517-525.
Cu(II) catalyzes the construction of 4,5-disubstituted 1,2,4-triazole-3-thiones from arylidenearylthiosemicarbazides. Upon prolonging the reaction time, the in situ generated thiones are transformed to 4,5-disubstituted 1,2,4-triazoles via a desulfurization process.
A. Gogoi, S. Guin, S. Rajamanickam, S. K. Rout, B. K. Patel, J. Org. Chem., 2015, 80, 9016-9027.
A series of new oxamide-derived amidine reagents can be accessed in excellent yield with minimal purification necessary. A subsequent reaction of these reagents with various hydrazine hydrochloride salts efficiently generates 1,5-disubstituted-1,2,4-triazole compounds in good yields. Both aromatic and aliphatic hydrazines react readily with the amidine reagents under very mild reaction conditions.
Y. Xu, M. McLaughlin, E. N. Bolton, R. A. Reamer, J. Org. Chem., 2010, 75, 8666-8669.
N-Tosylhydrazones can be used as substrates for diversity-oriented synthesis of 1,2,4-triazoles, 1,3,4-thiadiazoles, and 1,3,4-selenadiazoles with NH2CN, KOCN, KSCN, and KSeCN as odorless reaction partners. Reactions in the presence of NCS include an in situ formation of N-tosylhydrazonoyl chlorides.
Z. Wei, Q. Zhang, M. Tang, S. Zhang, Q. Zhang, Org. Lett., 2021, 23, 4420-4425.
3-N,N-Dialkylamino-1,2,4-triazoles can be prepared from S-methylisothioureas and acyl hydrazides in good yields. The reaction conditions are relatively mild and tolerate a broad range of functional groups.
D. V. Batchelor, D. M. Beal, T. B. Brown, D. Ellis, D. W. Gordon, P. S. Johnson, H. J. Mason, M. J. Ralph, T. J. Underwood, S. Wheeler, Synlett, 2008, 2421-2424.
I2-mediated oxidative C-N and N-S bond formations in water enable a metal-free, environmentally benign and convenient strategy for the synthesis of 4,5-disubstituted/N-fused 3-amino-1,2,4-triazoles and 3-substituted 5-amino-1,2,4-thiadiazoles from isothiocyanates. The scalable protocols exhibited excellent substrate tolerance.
N. Jatangi, N. Tumula, R. K. Palakodety, M. Nakka, J. Org. Chem., 2018, 83, 5715-5723.